- The figure shows express ACE2 receptors in lungs, heart, kidneys, intestines, brain, and testicles  
- (A) COVID-19 virus travel throughout the body via the bloodstream 
- (B) SARS-CoV-2 may reach the brain via circulation and/or an upper nasal trancribrial route 
- (C) SARS-CoV-2 virus bind and engage with the ACE2 receptors (D, blue). 
- (D) SARS-CoV-2 virus docks on the ACE2 via spike protein (D, golden spikes). 


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- The presence of the COVID-19 virus in the general circulation understandably enables it to pass into the cerebral circulation  (Figure 1A−C)
- Movement of the blood within the microcirculation could be one of the factors that may facilitate the interaction of the COVID-19 virus spike protein with ACE2 expressed in the capillary endothelium. 
- The budding of the viral particles from the capillary endothelium and damage to the endothelial lining can favor viral access to the brain (Figure 1B) 


Interaction Between Tissue Expression of ACE2 Receptors and SARS-CoV-2 Circulation.


ACE2 was found to be heavily expressed in the cell body of artificial, stem cell derived neurons, and less so in the axons and dendrites. Data from human brain tissue is yet to be collected, but these findings as well as other studies using mice brain tissue suggest that ACE2 expression in neurons could make them susceptible to SARS-CoV-2 infection.  

Neuronal ACE2 Expression as a Risk Factor for COVID-19

Baig, A. M., Khaleeq, A., Ali, U., & Syeda, H. (2020). Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host–virus interaction, and proposed neurotropic mechanisms. ACS chemical neuroscience, 11(7), 995-998.
https://pubs.acs.org/doi/abs/10.1021/acschemneuro.0c00122

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host−Virus Interaction, and Proposed Neurotropic Mechanisms

 (A) Sequence alignment of COVID-19 RBD subdomain-1 (319th to 591st) amino acid (top row) with the bat and SARS-CoV spike protein (middle and bottom row) that were fetched from BLASTp results of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acids. Note horizontal arrows that show areas of contrast between the sequences. (A1) Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template (6vsb.1. A)-based model of the COVID-19 virus spike glycoprotein. (B). Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template-(5x5b.1.A) based model of the prefusion structure of SARS-CoV spike glycoprotein in conformation 2 (B1) with 73.96% sequence identity. 


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